chr1-170719746-GA-G

Position:

• chr1-170719746-GA-G

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_022716.4(PRRX1):​c.269delA​(p.Lys90fs) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PRRX1 NM_022716.4 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 7.43

Genes affected

PRRX1 (HGNC:9142): (paired related homeobox 1) The DNA-associated protein encoded by this gene is a member of the paired family of homeobox proteins localized to the nucleus. The protein functions as a transcription co-activator, enhancing the DNA-binding activity of serum response factor, a protein required for the induction of genes by growth and differentiation factors. The protein regulates muscle creatine kinase, indicating a role in the establishment of diverse mesodermal muscle types. Alternative splicing yields two isoforms that differ in abundance and expression patterns. [provided by RefSeq, Jul 2008]

PRRX1 (HGNC:):

ACMG classification

Verdict is Pathogenic. Variant got 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 1-170719746-GA-G is Pathogenic according to our data. Variant chr1-170719746-GA-G is described in ClinVar as [Pathogenic]. Clinvar id is 50496.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRRX1	NM_022716.4	c.269delA	p.Lys90fs	frameshift_variant	2/4	ENST00000239461.11	NP_073207.1
PRRX1	NM_006902.5	c.269delA	p.Lys90fs	frameshift_variant	2/5		NP_008833.1
PRRX1	XM_006711388.4	c.128delA	p.Lys43fs	frameshift_variant	3/5		XP_006711451.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRRX1	ENST00000239461.11	c.269delA	p.Lys90fs	frameshift_variant	2/4	1	NM_022716.4	ENSP00000239461.6
PRRX1	ENST00000367760.7	c.269delA	p.Lys90fs	frameshift_variant	2/5	1		ENSP00000356734.3
PRRX1	ENST00000497230.2	c.269delA	p.Lys90fs	frameshift_variant	2/3	2		ENSP00000450762.1
PRRX1	ENST00000553786.1	n.379delA		non_coding_transcript_exon_variant	3/3	4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Agnathia-otocephaly complex Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Sep 01, 2012

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs398122375; hg19: chr1-170688887;